Bladder CancerBLADAPTNCT07043543
Evaluation of the Clinical Utility of Online Adaptive Radiotherapy in Bladder Cancer (BLADAPT-GETUG V11)
A study testing Adaptive radiotherapy and standard radiotherapy in people with Bladder Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 11 sites in France.
Trial summary
Trimodal therapy (TMT) consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy is a therapeutic alternative in patients with Muscle-Infiltrating Bladder Cancer who are inoperable or refuse surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Adaptive radiotherapy and standard radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 11 sitesFrance
- Study dates
- 15 Jan 2026to 30 Sep 2033
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven muscle-infiltrating bladder cancer (de novo MIBC or after a history of non-muscle-invasive bladder cancer) or patients with initial high-grade T1 tumor showing Ta or T1 recurrence, or those with high-grade T1 after a course of intravesical biological therapy or chemotherapy;
- Age ≥ 18 years;
- Urothelial carcinoma (transitional cell carcinoma of the bladder, micropapillary, microcystic with trophoblastic differenciation) and squamous cell histological types are allowed;
- Stage T1-T4aN0M0
- TransUrethral Resection of Bladder Tumor (TURBT) and Position Emission Tomography- scanner and X-ray Computed Tomography (PET-CT) or Computed Tomography scan of thorax/abdomen/pelvis (without carcinological anomaly) within 8 weeks prior to the start of radiation therapy (if TURBT was performed more than 6 weeks before the inclusion visit, a new TURBT or, at least, a cystoscopy showing no progression, no residual tumour or regrowth must be done);
- Suitable for radiotherapy;
Show all 11Show fewer
- Eastern Cooperative Oncology Group/World Human Organisation (ECOG/WHO) performance status from 0 to 2
- Negative pregnancy test (blood or urine), for women of childbearing age only;
- If the patient is sexually active, he/she must agree to use contraception deemed adequate and appropriate by the investigator throughout the period of study drug administration and 6 months after the end of treatment for both men and women.
- Affiliation to the French Social Security System;
- Dated, written and signed Informed consent
Who cannot join
- Prior pelvic radiation therapy;
- Patients with previous or concomitant other malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years;
- Presence of endopenic stent;
- Inability to comply with the protocol;
- Grade 1 or greater baseline diarrhea;
- Uncontrolled inflammatory bowel disease (ulcerative colitis or Crohn's disease);
Show all 10Show fewer
- Uncontrolled immune or cardiac or pulmonary disease;
- Patients whose regular follow-up is impossible for psychological, family, social or geographical reasons;
- Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study;
- Pregnant or breast-feeding subjects
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
France11 sites
Institut Sainte Catherine
Avignon, Var, 84000
Nathalie ROUARD, MD, 0490276233 ext. +33, n.rouard@isc84.org
Centre Georges François Leclerc
Dijon, Côte d'or, 21079
Magalie QUIVRIN, MD, 0380737518 ext. +33, mquivrin@cgfl.fr
Centre Oscar Lambret
Lille, Nord, 59000
David PASQUIER, MD, d-pasquier@o-lambret.fr
Institut du Cancer de Montpellier
Montpellier, Herault, 34298
Olivier RIOU, MD, 0467612443 ext. +33, olivier.riou@icm.unicancer.fr
Hôpital Tenon
Paris, Île-de-France Region, 75020
Laurie MONNIER, MD, 0142496059 ext. +33, laurie.monnier@aphp.fr
Centre Eugène Marquis
Rennes, Ille et Vilaine, 35000
Ingrid MASSON, MD, i.masson@rennes.unicancer.fr
Centre Henri Becquerel
Rouen, Seine Maritime, 76038
Ahmed BENYOUCEF, MD, ahmed.benyoucef@chb.unicancer.fr
Institut Curie
Saint-Cloud, Île-de-France Region, 92210
Gilles CREHANGE, MD, gilles.crehange@curie.fr
Institut de Cancérologie de l'Ouest
Saint-Herblain, Loire Atlantique, 44800
Stéphane SUPIOT, MD, 0240679913 ext. +33, stephane.supiot@ico.unicancer.fr
Centre de radiothérapie Saint-Louis
Toulon, Var, 83100
thomas DUBERGE, MD, 0494244050 ext. +33, tduberge@yahoo.fr
Centre de radiothérapie Bayard
Villeurbanne, Rhone, 69100
Victor PASSERAT, MD, 0426686767 ext. +33, passerat.bayard@orange.fr
About this study
Official title: Randomized Open Phase II Multienter Study Evaluating the Clinical Utility of Online Adaptive Radiotherapy in Bladder Cancer
Trimodal therapy (TMT) consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy is a therapeutic alternative in patients with Muscle-Infiltrating Bladder Cancer who are inoperable or refuse surgery. One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during and between radiotherapy sessions. Standard radiotherapy techniques require large planning target volume margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities.
Adaptive radiotherapy allows for the generation of a treatment fraction personalized to a patient's anatomical modification with margin reduction and improves the dosimetric quality of the delivered plans.
The hypothesis is that this improvement results in radiation-induced toxicity improvement.
Read the detailed description
In 2023, the incidence of muscle-infiltrating bladder cancer (MIBC) in France was 14062 cases, 81% of which were in men.
The standard treatment for MIBC is cystectomy preceded by neoadjuvant chemotherapy. Trimodal therapy (TMT), consisting of transurethral resection of bladder tumors (TURBT) followed by radiotherapy (RT) and chemotherapy (CT), has emerged as a valuable therapeutic de-escalation alternative in patients who are inoperable or refuse surgery with its physical and psychological sequelae. TMT provides survival outcomes identical to cystectomy in selected patients and allows for bladder preservation in successful cases. TMT is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder who failed intravesical therapy.
One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during radiotherapy sessions (intra-fractional movement) and between sessions (inter-fractional movement). To take into account these movements, standard radiotherapy techniques require large planning target volume (PTV) margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities up to 42% and 17% respectively.
Adaptive radiotherapy (ART) allows for the generation of a treatment fraction personalized to a patient's anatomical modification. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible to perform a daily customization of the radiotherapy session ("online") for a given patient to ensure optimal coverage of the target with minimized margins. ART allows PTV margins reduction for MIBC and improves therefore the dosimetric quality of the delivered plans.
The hypothesis is that the dosimetric improvement induced by ART results in radiation-induced toxicity improvement.
- Conditions
- Bladder Cancer
- Being tested
- Adaptive radiotherapy, standard radiotherapy
- Keywords
- Adaptive radiotherapy, standard radiotherapy, Tri-Modal therapy
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adaptive radiotherapyRadiation
Patient will be treated by concomitant:
- adaptive radiotherapy 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB).
- chemotherapy if not contraindicated :
- Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or
- Gemcitabine: 80 to 100 mg/m2/week Or
- Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy)
standard radiotherapyRadiation
Patient will be treated by concomitant:
- standard 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB).
- chemotherapy if not contraindicated :
- Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or
- Gemcitabine: 80 to 100 mg/m2/week Or
- Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy)
| Study group | Role | What they receive |
|---|---|---|
| experimental arm | Experimental | Adaptive radiotherapy +/- chemotherapy Receives: Radiation: Adaptive radiotherapy |
| standard arm | Active comparator | Standard radiotherapy +/- chemotherapy Receives: Radiation: standard radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity.
rate of patients without acute diarrhea grade ≥2
Measured: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
Secondary outcomes (12)
Evaluation of all acute toxicities
description of all acute toxicities according to Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0)
Measured: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
Evaluation of all late toxicities
description of all late toxicities according to Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0)
Measured: from 3 months after the last day of Radiotherapy to 5 years after the last day of Radiotherapy
evaluation of quality of life specific to the cancer disease
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire (EORTC QLQ-C30)
Measured: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life and of the measurements specific to the treatment of bladder cancer with muscle invasion
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire - Bladder Cancer (EORTC QLQ-BLM30)
Measured: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old in order to establish a minimum standardized geriatric assessment
Quality of life will be evaluated using Geriatric COre DatasEt oncogeriatric (GCODE) for patient ≥ 70 years old
Measured: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old (Specific to elderly people with cancer)
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire-Elderly (EORTC QLQ- ELD30) for patient ≥ 70 years old
Measured: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
assessment of disease free survival
time interval from randomization to first carcinologic event as local or distant relapse or death
Measured: At 3 and 5 years after the last day of Radiotherapy
assessment of cystectomy free survival
the time interval from randomization to cystectomy
Measured: At 3 and 5 years after the last day of Radiotherapy
assessment of overall survival
the time interval from randomization to death from any cause
Measured: At 3 and 5 years after the last day of Radiotherapy
assessment of local control rate
The presence of non-muscle-invasive or muscle-invasive bladder cancers evaluate by cystoscopy
Measured: At 3 and 5 years after the last day of Radiotherapy
assessment of the dosimetric results
Dosimetric results in terms of treatment volume coverage and Organ At Risk protection
Measured: during tthe radiotherapy for both arms
evaluation of the impact of the adaptive process on fractions execution
Evaluation of duration of the treatment fractions (in minutes) in the two arms. Evaluation of the percentage of fractions fully delivered and the duration of physician/physicist mobilization for the adaptive process
Measured: during tthe radiotherapy for both arms
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2025
- Study start15 Jan 2026 (estimated)
- Primary completion30 Jan 2029 (estimated)
- Study completion30 Sep 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (42)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ligue contre le cancer, France
- Responsible party
- Sponsor
- Investigators
- Olivier RIOU, MD, Principal investigator, INSTITUT REGIONAL DU CANCER DE MONTPELLIER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07043543
- Sponsor's protocol ID
- PROICM 2024-02 BLA
- Acronym
- BLADAPT
- Status last verified
- Dec 2025
- First submitted
- 17 Jun 2025
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cabaille M, Khalifa J, Tessier AM, Belhomme S, Crehange G, Sargos P. [A review of adaptive radiotherapy for bladder cancer]. Cancer Radiother. 2021 May;25(3):271-278. doi: 10.1016/j.canrad.2020.08.046. Epub 2021 Jan 2. French.
PubMed 33402293Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kubler H, Stenzl A, Gakis G. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol. 2018 Feb;36(2):43-53. doi: 10.1016/j.urolonc.2017.10.002. Epub 2017 Nov 6.
PubMed 29102254Huddart R, Hafeez S, Omar A, Alonzi R, Birtle A, Cheung KC, Choudhury A, Foroudi F, Gribble H, Henry A, Hilman S, Hindson B, Lewis R, Muthukumar D, McLaren DB, McNair H, Nikapota A, Olorunfemi A, Parikh O, Philipps L, Rimmer Y, Syndikus I, Tolentino A, Varughese M, Vassallo-Bonner C, Webster A, Griffin C, Hall E. Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial. Clin Oncol (R Coll Radiol). 2023 Sep;35(9):586-597. doi: 10.1016/j.clon.2023.05.002. Epub 2023 May 9.
PubMed 37225552Hafeez S, Lewis R, Hall E, Huddart R; RAIDER Trial Management Group. Advancing Radiotherapy for Bladder Cancer: Randomised Phase II Trial of Adaptive Image-guided Standard or Dose-escalated Tumour Boost Radiotherapy (RAIDER). Clin Oncol (R Coll Radiol). 2021 Jun;33(6):e251-e256. doi: 10.1016/j.clon.2021.02.012. Epub 2021 Mar 23. No abstract available.
PubMed 33766502Kool R, Dragomir A, Kulkarni GS, Marcq G, Breau RH, Kim M, Busca I, Abdi H, Dawidek M, Uy M, Fervaha G, Cury FL, Alimohamed N, Izawa J, Jeldres C, Rendon R, Shayegan B, Siemens R, Black PC, Kassouf W. Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis. Eur Urol Oncol. 2024 Dec;7(6):1350-1357. doi: 10.1016/j.euo.2024.01.014. Epub 2024 Feb 6.
PubMed 38326142Dahl DM, Rodgers JP, Shipley WU, Michaelson MD, Wu CL, Parker W, Jani AB, Cury FL, Hudes RS, Michalski JM, Hartford AC, Song D, Citrin DE, Karrison TG, Sandler HM, Feng FY, Efstathiou JA. Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024 Dec;42(34):4095-4102. doi: 10.1200/JCO.23.02510. Epub 2024 Sep 3.
PubMed 39226514de Haar-Holleman A, van Hoogstraten LMC, Hulshof MCCM, Tascilar M, Bruck K; BlaZIB study group; Meijer RP, Alfred Witjes J, Kiemeney LA, Aben KKH. Chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine: A nationwide cohort study. Radiother Oncol. 2023 Jun;183:109584. doi: 10.1016/j.radonc.2023.109584. Epub 2023 Mar 1.
PubMed 36863459Hall E, Hussain SA, Porta N, Lewis R, Crundwell M, Jenkins P, Rawlings C, Tremlett J, Sreenivasan T, Wallace J, Syndikus I, Sheehan D, Lydon A, Huddart R, James N; BC2001 Investigators. Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. Eur Urol. 2022 Sep;82(3):273-279. doi: 10.1016/j.eururo.2022.04.017. Epub 2022 May 14.
PubMed 35577644Sibolt P, Andersson LM, Calmels L, Sjostrom D, Bjelkengren U, Geertsen P, Behrens CF. Clinical implementation of artificial intelligence-driven cone-beam computed tomography-guided online adaptive radiotherapy in the pelvic region. Phys Imaging Radiat Oncol. 2020 Dec 18;17:1-7. doi: 10.1016/j.phro.2020.12.004. eCollection 2021 Jan.
PubMed 33898770Hussain MH, Glass TR, Forman J, Sakr W, Smith DC, Al-Sarraf M, Jones J, Balcerzak SP, Crawford ED, Grossman HB. Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study. J Urol. 2001 Jan;165(1):56-60; discussion 60-1. doi: 10.1097/00005392-200101000-00014.
PubMed 11125363Azria D, Riou O, Rebillard X, Thezenas S, Thuret R, Fenoglietto P, Pouessel D, Culine S. Combined chemoradiation therapy with twice-weekly gemcitabine and cisplatin for organ preservation in muscle-invasive bladder cancer: long-term results of a phase 1 trial. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):853-9. doi: 10.1016/j.ijrobp.2013.11.016. Epub 2013 Dec 21.
PubMed 24368064Housset M, Maulard C, Chretien Y, Dufour B, Delanian S, Huart J, Colardelle F, Brunel P, Baillet F. Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. J Clin Oncol. 1993 Nov;11(11):2150-7. doi: 10.1200/JCO.1993.11.11.2150.
PubMed 8229129Oh KS, Soto DE, Smith DC, Montie JE, Lee CT, Sandler HM. Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial. Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):511-7. doi: 10.1016/j.ijrobp.2008.08.021. Epub 2008 Oct 30.
PubMed 18977098Kent E, Sandler H, Montie J, Lee C, Herman J, Esper P, Fardig J, Smith DC. Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial. J Clin Oncol. 2004 Jul 1;22(13):2540-5. doi: 10.1200/JCO.2004.10.070.
PubMed 15226322Caffo O, Thompson C, De Santis M, Kragelj B, Hamstra DA, Azria D, Fellin G, Pappagallo GL, Galligioni E, Choudhury A. Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials. Radiother Oncol. 2016 Nov;121(2):193-198. doi: 10.1016/j.radonc.2016.09.006. Epub 2016 Oct 5.
PubMed 27720221
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Open Phase II Multienter Study Evaluating the Clinical Utility of Online Adaptive Radiotherapy in Bladder Cancer
- ClinicalTrials.gov ID
- NCT07043543
- Acronym / sponsor ID
- BLADAPT / PROICM 2024-02 BLA
- Conditions
- Bladder Cancer
- Keywords
- Adaptive radiotherapy, standard radiotherapy, Tri-Modal therapy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Collaborators
- Ligue contre le cancer, France
- Study start
- 15 Jan 2026 (estimated)
- Primary completion
- 30 Jan 2029 (estimated)
- Study completion
- 30 Sep 2033 (estimated)
- First posted
- 29 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Trimodal therapy (TMT) consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy is a therapeutic alternative in patients with Muscle-Infiltrating Bladder Cancer who are inoperable or refuse surgery. One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during and between radiotherapy sessions. Standard radiotherapy techniques require large planning target volume margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities.
Adaptive radiotherapy allows for the generation of a treatment fraction personalized to a patient's anatomical modification with margin reduction and improves the dosimetric quality of the delivered plans.
The hypothesis is that this improvement results in radiation-induced toxicity improvement.
Detailed description
In 2023, the incidence of muscle-infiltrating bladder cancer (MIBC) in France was 14062 cases, 81% of which were in men.
The standard treatment for MIBC is cystectomy preceded by neoadjuvant chemotherapy. Trimodal therapy (TMT), consisting of transurethral resection of bladder tumors (TURBT) followed by radiotherapy (RT) and chemotherapy (CT), has emerged as a valuable therapeutic de-escalation alternative in patients who are inoperable or refuse surgery with its physical and psychological sequelae. TMT provides survival outcomes identical to cystectomy in selected patients and allows for bladder preservation in successful cases. TMT is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder who failed intravesical therapy.
One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during radiotherapy sessions (intra-fractional movement) and between sessions (inter-fractional movement). To take into account these movements, standard radiotherapy techniques require large planning target volume (PTV) margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities up to 42% and 17% respectively.
Adaptive radiotherapy (ART) allows for the generation of a treatment fraction personalized to a patient's anatomical modification. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible to perform a daily customization of the radiotherapy session ("online") for a given patient to ensure optimal coverage of the target with minimized margins. ART allows PTV margins reduction for MIBC and improves therefore the dosimetric quality of the delivered plans.
The hypothesis is that the dosimetric improvement induced by ART results in radiation-induced toxicity improvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| experimental arm | Experimental | Radiation: Adaptive radiotherapyAdaptive radiotherapy +/- chemotherapy |
| standard arm | Active comparator | Radiation: standard radiotherapyStandard radiotherapy +/- chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically proven muscle-infiltrating bladder cancer (de novo MIBC or after a history of non-muscle-invasive bladder cancer) or patients with initial high-grade T1 tumor showing Ta or T1 recurrence, or those with high-grade T1 after a course of intravesical biological therapy or chemotherapy;
- Age ≥ 18 years;
- Urothelial carcinoma (transitional cell carcinoma of the bladder, micropapillary, microcystic with trophoblastic differenciation) and squamous cell histological types are allowed;
- Stage T1-T4aN0M0
- TransUrethral Resection of Bladder Tumor (TURBT) and Position Emission Tomography- scanner and X-ray Computed Tomography (PET-CT) or Computed Tomography scan of thorax/abdomen/pelvis (without carcinological anomaly) within 8 weeks prior to the start of radiation therapy (if TURBT was performed more than 6 weeks before the inclusion visit, a new TURBT or, at least, a cystoscopy showing no progression, no residual tumour or regrowth must be done);
Key exclusion criteria (10 listed)
- Prior pelvic radiation therapy;
- Patients with previous or concomitant other malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years;
- Presence of endopenic stent;
- Inability to comply with the protocol;
- Grade 1 or greater baseline diarrhea;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adaptive radiotherapyPatient will be treated by concomitant: * adaptive radiotherapy 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB). * chemotherapy if not contraindicated : * Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or * Gemcitabine: 80 to 100 mg/m2/week Or * Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy) | Radiation | experimental arm |
| standard radiotherapyPatient will be treated by concomitant: * standard 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB). * chemotherapy if not contraindicated : * Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or * Gemcitabine: 80 to 100 mg/m2/week Or * Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy) | Radiation | standard arm |
Primary outcome
evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity.
Time frame: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
rate of patients without acute diarrhea grade ≥2
12 secondary outcomes
Evaluation of all acute toxicities
Time frame: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
Evaluation of all late toxicities
Time frame: from 3 months after the last day of Radiotherapy to 5 years after the last day of Radiotherapy
evaluation of quality of life specific to the cancer disease
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life and of the measurements specific to the treatment of bladder cancer with muscle invasion
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old in order to establish a minimum standardized geriatric assessment
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old (Specific to elderly people with cancer)
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
assessment of disease free survival
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of cystectomy free survival
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of overall survival
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of local control rate
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of the dosimetric results
Time frame: during tthe radiotherapy for both arms
evaluation of the impact of the adaptive process on fractions execution
Time frame: during tthe radiotherapy for both arms
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Background: PubMed 33402293Cabaille M, Khalifa J, Tessier AM, Belhomme S, Crehange G, Sargos P. [A review of adaptive radiotherapy for bladder cancer]. Cancer Radiother. 2021 May;25(3):271-278. doi: 10.1016/j.canrad.2020.08.046. Epub 2021 Jan 2. French.
- Background: PubMed 29102254Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kubler H, Stenzl A, Gakis G. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol. 2018 Feb;36(2):43-53. doi: 10.1016/j.urolonc.2017.10.002. Epub 2017 Nov 6.
- Background: PubMed 37225552Huddart R, Hafeez S, Omar A, Alonzi R, Birtle A, Cheung KC, Choudhury A, Foroudi F, Gribble H, Henry A, Hilman S, Hindson B, Lewis R, Muthukumar D, McLaren DB, McNair H, Nikapota A, Olorunfemi A, Parikh O, Philipps L, Rimmer Y, Syndikus I, Tolentino A, Varughese M, Vassallo-Bonner C, Webster A, Griffin C, Hall E. Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial. Clin Oncol (R Coll Radiol). 2023 Sep;35(9):586-597. doi: 10.1016/j.clon.2023.05.002. Epub 2023 May 9.
- Background: PubMed 33766502Hafeez S, Lewis R, Hall E, Huddart R; RAIDER Trial Management Group. Advancing Radiotherapy for Bladder Cancer: Randomised Phase II Trial of Adaptive Image-guided Standard or Dose-escalated Tumour Boost Radiotherapy (RAIDER). Clin Oncol (R Coll Radiol). 2021 Jun;33(6):e251-e256. doi: 10.1016/j.clon.2021.02.012. Epub 2021 Mar 23. No abstract available.
- Background: PubMed 38326142Kool R, Dragomir A, Kulkarni GS, Marcq G, Breau RH, Kim M, Busca I, Abdi H, Dawidek M, Uy M, Fervaha G, Cury FL, Alimohamed N, Izawa J, Jeldres C, Rendon R, Shayegan B, Siemens R, Black PC, Kassouf W. Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis. Eur Urol Oncol. 2024 Dec;7(6):1350-1357. doi: 10.1016/j.euo.2024.01.014. Epub 2024 Feb 6.
- Background: PubMed 39226514Dahl DM, Rodgers JP, Shipley WU, Michaelson MD, Wu CL, Parker W, Jani AB, Cury FL, Hudes RS, Michalski JM, Hartford AC, Song D, Citrin DE, Karrison TG, Sandler HM, Feng FY, Efstathiou JA. Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024 Dec;42(34):4095-4102. doi: 10.1200/JCO.23.02510. Epub 2024 Sep 3.
- Background: PubMed 36863459de Haar-Holleman A, van Hoogstraten LMC, Hulshof MCCM, Tascilar M, Bruck K; BlaZIB study group; Meijer RP, Alfred Witjes J, Kiemeney LA, Aben KKH. Chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine: A nationwide cohort study. Radiother Oncol. 2023 Jun;183:109584. doi: 10.1016/j.radonc.2023.109584. Epub 2023 Mar 1.
- Background: PubMed 35577644Hall E, Hussain SA, Porta N, Lewis R, Crundwell M, Jenkins P, Rawlings C, Tremlett J, Sreenivasan T, Wallace J, Syndikus I, Sheehan D, Lydon A, Huddart R, James N; BC2001 Investigators. Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. Eur Urol. 2022 Sep;82(3):273-279. doi: 10.1016/j.eururo.2022.04.017. Epub 2022 May 14.
- Background: PubMed 33898770Sibolt P, Andersson LM, Calmels L, Sjostrom D, Bjelkengren U, Geertsen P, Behrens CF. Clinical implementation of artificial intelligence-driven cone-beam computed tomography-guided online adaptive radiotherapy in the pelvic region. Phys Imaging Radiat Oncol. 2020 Dec 18;17:1-7. doi: 10.1016/j.phro.2020.12.004. eCollection 2021 Jan.
- Background: PubMed 11125363Hussain MH, Glass TR, Forman J, Sakr W, Smith DC, Al-Sarraf M, Jones J, Balcerzak SP, Crawford ED, Grossman HB. Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study. J Urol. 2001 Jan;165(1):56-60; discussion 60-1. doi: 10.1097/00005392-200101000-00014.
- Background: PubMed 24368064Azria D, Riou O, Rebillard X, Thezenas S, Thuret R, Fenoglietto P, Pouessel D, Culine S. Combined chemoradiation therapy with twice-weekly gemcitabine and cisplatin for organ preservation in muscle-invasive bladder cancer: long-term results of a phase 1 trial. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):853-9. doi: 10.1016/j.ijrobp.2013.11.016. Epub 2013 Dec 21.
- Background: PubMed 8229129Housset M, Maulard C, Chretien Y, Dufour B, Delanian S, Huart J, Colardelle F, Brunel P, Baillet F. Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. J Clin Oncol. 1993 Nov;11(11):2150-7. doi: 10.1200/JCO.1993.11.11.2150.
- incidence et de la mortalité par cancer en France métropolitaineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Olivier RIOU, MD principal investigator
INSTITUT REGIONAL DU CANCER DE MONTPELLIER
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Adaptive radiotherapy and standard radiotherapy in people with Bladder Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aurore MOUSSION (467613102 ext. +33, aurore.moussion@icm.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity. (time frame: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07043543, which also lists 42 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.